The show's pilot episode premiered on September 24, 2007. This was the second pilot produced for the show. A different pilot was produced for the 2006–07 television season but never aired. The structure of the original unaired pilot was substantially different from the series' current form. The only main characters retained in both pilots were Leonard (Johnny Galecki) and Sheldon (Jim Parsons), who are named after Sheldon Leonard, a longtime figure in episodic television as producer, director and actor. A minor character, Althea (Vernee Watson), appeared in the first scene of both pilots that was retained generally as-is. The first pilot included two female lead characters - Katie, "a street-hardened, tough-as-nails woman with a vulnerable interior" (played by Canadian actress Amanda Walsh) and Gilda, a scientist colleague and friend of the male characters (played by Iris Bahr). Sheldon and Leonard meet Katie after she breaks up with a boyfriend and they invite her to share their apartment. Gilda is threatened by Katie's presence. Test audiences reacted negatively to Katie, but they liked Sheldon and Leonard. The original pilot used Thomas Dolby's hit "She Blinded Me with Science" as its theme song.
David Saltzberg, a professor of physics and astronomy at the University of California, Los Angeles, checks scripts and provides dialogue, mathematics equations, and diagrams used as props. According to executive producer/co-creator Bill Prady, "We're working on giving Sheldon an actual problem that he's going to be working on throughout the [first] season so there's actual progress to the boards ... . We worked hard to get all the science right." David Saltzberg, who has a Ph.D. in physics, has served as the science consultant for the show for six seasons and attends every taping. He sees early versions of scripts which need scientific information added to them, and he also points out where the writers, despite their knowledge of science, have made a mistake. He is usually not needed during a taping unless a lot of science, and especially the whiteboard, is involved.
Jim Parsons as Sheldon Cooper: Originally from Galveston, Texas, Sheldon was a child prodigy with an eidetic memory who began college at the age of eleven, and earned a PhD at age sixteen. He is a theoretical physicist researching quantum mechanics and string theory, and despite his IQ of 187, he finds many routine aspects of social situations difficult to grasp. He is determined to have his own way, continually boasts of his intelligence, and has an extremely ritualized way of living. Despite these quirks, he begins a relationship with Amy Farrah Fowler, and they eventually marry.
Sheldon and Amy are surprised to find that Wil Wheaton's new Professor Proton show is actually very entertaining and that Wil had Howard on as a guest. On Howard's suggestion, Sheldon apologizes to Wil, mending their friendship, and tells him he wants to be on the show; but Wil asks for Amy. Sheldon tells her to do it, but she says she often doesn't do things to avoid upsetting him. Sheldon is horrified when he realises how selfish he has been, especially when he finds out that the men do the same for him. Sheldon encourages Amy to go on the show to inspire girls to pursue science while trying to control his obvious jealousy for her. Meanwhile, Leonard writes a book about a physicist that solves a murder, the protagonist Logan Dean is based on himself. Bernadette points out Logan's mean boss Illsa is similar to Penny, who thinks it is based on Bernadette, though Leonard does not correct her. However, Bernadette tells Penny the truth, upsetting her and making her mad at Leonard. After calling his mother for advice, Leonard learns that Illsa is actually like her; but abandons the book when he realizes he wrote romantic tension into the relationship between the characters.